MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3
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Zhongyi Fan1,*, Hanzhi Cui2,*, Xiaojie Xu3,*, Zhi Lin1, Xuelin Zhang1, Lei Kang4, Baiyu Han5, Jing Meng1, Zhifeng Yan1, Xiang Yan1, Shunchang Jiao1
1Department of Oncology, PLA General Hospital, Beijing, China
2Department of Oncology, 309th Hospital of PLA, Beijing, China
3Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China
4Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
5Department of Endocrinology and Metablism, 264th Hospital of PLA, Shanxi, China
*These authors have contributed equally to this work
Shunchang Jiao, e-mail: [email protected]
Keywords: miR-125a, cervical cancer, cell growth, metastasis, STAT3
Received: March 23, 2015 Accepted: June 30, 2015 Published: July 13, 2015
MiR-125a has been characterized as a tumor suppressor in several cancers. However, the role of miR-125a in cervical cancer is unknown. In this study, we found the expression of miR-125a was downregulated in cervical cancer patients, and negatively correlated with the tumor size, FIGO stage, and preoperative metastasis. Kaplan-Meier analysis showed that miR-125a expression predicted favorable outcome for cervical cancer patients. Dual luciferase assays identified the STAT3 gene as a novel direct target of miR-125a. Functional studies showed that miR-125a overexpression significantly suppressed the growth, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells both in vitro and in vivo via decreasing STAT3 expression. Moreover, miR-125a conferred to G2/M cell cycle arrest, accompanied by inhibition of several G2/M checkpoint proteins. Mechanistically, inactivation of miR-125a during cervical carcinogenesis was caused by HPV suppression of p53 expression. Clinically, STAT3, the expression of which, predicted poorer outcome, was inversely correlated with miR-125a in cervical cancer. These data highlight the importance of miR-125a in the cell proliferation and progression of cervical cancer, and indicate that miR-125a may be a useful therapeutic target for cervical cancer.
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